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Ketogenic Diet Compromises Both Cancellous and Cortical Bone Mass in Mice

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Abstract

To clarify osteoporotic effects of ketogenic diet (KD) on cancellous and cortical bone compared with ovariectomy (OVX) in mice. Forty female C57BL/6J 8-week-old mice were randomly divided into SD+Sham, SD+OVX, KD+Sham, and KD+OVX groups, and fed for 12 weeks. The distal femur of trabecular bone and the middle femur of cortical bone were evaluated with Micro-CT scanning. The maximum bending force and stiffness of the tibia were calculated using a three-point bending test. Osteoblast and osteoclast expression of femur were identified using tartrate-resistant acid phosphatase (TRAP), collagen type I (CoLI), and osteocalcin (OCN) staining. A 2-factor analysis of variance was used to evaluate effects of KD and OVX on radiological, biomechanical, and histological parameters. KD resulted in not only remarkable cancellous bone decline comparable to OVX, but also unique cortical bone reduction. The maximum bending force and stiffness decreased in the KD+Sham and KD+OVX groups but did not change in the SD+OVX group. The KD+OVX led to significantly higher expression in TRAP and noticeably lower expression in CoLI when compared with other groups. Both KD+Sham and SD+OVX prominently increased expression in TRAP, but decreased expression in CoLI. There was no significant difference in OCN among the four groups. The present results suggest that KD compromises both the cancellous and cortical bone architecture of long bones while OVX only in cancellous bone architecture. A combination of KD and OVX may lead to more bone loss.

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Acknowledgements

This study is supported by National Natrual Science Foundation of China (No. 81472084). We like to thank Professor Ping Liang at Southern Hospital of Southern Medical University for his help in revising the manuscript, and Dr. Bin Huang, Song Xu, and Wenhao Wang at Southern Medical University for their help in histological analysis.

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Authors and Affiliations

  1. Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China

    Xiuhua Wu, Zucheng Huang, Junhao Liu, Zhiping Huang, Ganggang Kong, Xiaolin Xu, Jianyang Ding & Qingan Zhu

  2. Department of Spinal Surgery, LongYan First Hospital, Longyan, Fujian, China

    Xiaomeng Wang

  3. Department of Spinal Surgery, Affiliated Jiangmen Hospital of Sun Yat Sen University, Jiangmen, Guangdong, China

    Zhaozong Fu

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  1. Xiuhua Wu
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Contributions

Author Contributions

QZ and XW designed the experiments. XW, XW, and ZH conducted the animal experiments. XW, ZH, ZF, and XX wrote the manuscript. XW, JL, GK, and JD completed the data analysis, and QZ revised the manuscript.

Corresponding author

Correspondence to Qingan Zhu.

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Conflict of interest

Xiuhua Wu, Zucheng Huang, Xiaomeng Wang, Zhaozong Fu, Junhao Liu, Zhiping Huang, Ganggang Kong, Xiaolin Xu, Jianyang Ding, and Qingan Zhu, declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

The present study was approved by the Animal Experiments Ethics Committee of Southern Medical University. The animal procedures were conducted in accordance with the Guidelines of Caring for Laboratory Animals by the Ministry of Science and Technology of the People’s Republic of China. Surgery was performed under anesthesia, and all efforts were made to minimize suffering.

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Wu, X., Huang, Z., Wang, X. et al. Ketogenic Diet Compromises Both Cancellous and Cortical Bone Mass in Mice. Calcif Tissue Int 101, 412–421 (2017). https://doi.org/10.1007/s00223-017-0292-1

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  • DOI: https://doi.org/10.1007/s00223-017-0292-1

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